Scholarlink

<p>Macrophage polarization is critically involved in the initiation and progression of ulcerative colitis (UC); however, whether microvesicles (MVs) released from macrophages with distinct polarization states exert different effects on the intestinal epithelial barrier and endoplasmic reticulum (ER) stress remains unclear. Here, MVs were isolated from M0, M1, and M2 macrophages and evaluated in a dextran sulfate sodium (DSS)-induced mouse colitis model and an inflammatory cytokine-stimulated NCM460 epithelial cell model. M2 macrophage-derived MVs (M2-MVs) mitigated body-weight loss, disease activity, colon shortening, and histopathological injury and partially restored Claudin-1, Occludin, ZO-1, and MUC2 expression. In contrast, M1 macrophage-derived MVs (M1-MVs) tended to aggravate inflammation and barrier disruption. Mechanistically, M2-MVs reduced IL-1β, TNF-α, and IL-6, increased IL-10, and inhibited GRP78, PERK/eIF2α phosphorylation, CHOP, and cleaved caspase-3. Consistent effects were observed in vitro, where M2-MVs restored barrier proteins and reduced ER stress and apoptosis. Moreover, the ER-stress inhibitor 4-phenylbutyric acid attenuated the detrimental effects of M1-MVs, supporting ER stress as an important downstream mechanism. By systematically comparing MVs from M0, M1, and M2 macrophages in parallel, this study reveals a polarization-dependent, bidirectional pattern of macrophage–epithelial communication in experimental colitis and provides preclinical evidence supporting M2-MVs as candidate cell-free effectors for intestinal mucosal repair.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Polarized macrophage-derived microvesicles differentially modulate intestinal barrier dysfunction and endoplasmic reticulum stress in ulcerative colitis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年8月3日

查看全文
  • Chaoyue Liang,
  • Qasim Khan,
  • Yanling Wei,
  • Sha Wang,
  • Han Wei,
  • Yuyang Jia,
  • Yanqiu Xu,
  • Cuihua Qi

摘要

Macrophage polarization is critically involved in the initiation and progression of ulcerative colitis (UC); however, whether microvesicles (MVs) released from macrophages with distinct polarization states exert different effects on the intestinal epithelial barrier and endoplasmic reticulum (ER) stress remains unclear. Here, MVs were isolated from M0, M1, and M2 macrophages and evaluated in a dextran sulfate sodium (DSS)-induced mouse colitis model and an inflammatory cytokine-stimulated NCM460 epithelial cell model. M2 macrophage-derived MVs (M2-MVs) mitigated body-weight loss, disease activity, colon shortening, and histopathological injury and partially restored Claudin-1, Occludin, ZO-1, and MUC2 expression. In contrast, M1 macrophage-derived MVs (M1-MVs) tended to aggravate inflammation and barrier disruption. Mechanistically, M2-MVs reduced IL-1β, TNF-α, and IL-6, increased IL-10, and inhibited GRP78, PERK/eIF2α phosphorylation, CHOP, and cleaved caspase-3. Consistent effects were observed in vitro, where M2-MVs restored barrier proteins and reduced ER stress and apoptosis. Moreover, the ER-stress inhibitor 4-phenylbutyric acid attenuated the detrimental effects of M1-MVs, supporting ER stress as an important downstream mechanism. By systematically comparing MVs from M0, M1, and M2 macrophages in parallel, this study reveals a polarization-dependent, bidirectional pattern of macrophage–epithelial communication in experimental colitis and provides preclinical evidence supporting M2-MVs as candidate cell-free effectors for intestinal mucosal repair.